Ask about this productRelated genes to: DDHD2 Blocking Peptide
- Gene:
- DDHD2 NIH gene
- Name:
- DDHD domain containing 2
- Previous symbol:
- SAMWD1
- Synonyms:
- KIAA0725, SPG54
- Chromosome:
- 8p11.23
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-23
- Date modifiied:
- 2018-11-15
Related products to: DDHD2 Blocking Peptide
Related articles to: DDHD2 Blocking Peptide
- Luminal breast cancer is characterized by a persistent risk of recurrence and dysregulated lipid metabolism. However, the role of phase separation, a novel mechanism for the spatial compartmentalization of proteins, in lipid remodeling within the context of breast cancer remains largely unexplored. Utilizing the multiomics data from our large breast cancer cohort (n = 773), we revealed that aberrant lipid metabolism negatively impacts the prognosis of patients with luminal breast cancer. Furthermore, we deciphered that the copy number alteration-driven -regulation of DDHD domain containing 2 (DDHD2) is correlated with lipid remodeling in luminal breast cancer. Mechanistically, DDHD2 forms biomolecular condensates through phase separation upon AKT1-mediated phosphorylation, which enhances its lipase activity, reduces the abundance of proferroptotic lipids, and consequently decreases ferroptosis susceptibility. Therapeutically, the DDHD2 inhibitor KLH45 remarkably enhances ferroptosis sensitivity to restrict luminal breast cancer progression, and its combination with ferroptosis inducers further improves the efficacy of endocrine therapy. Collectively, our findings reveal a key role of DDHD2 condensates in lipid reprogramming and propose an innovative therapeutic strategy for luminal breast cancer. - Source: PubMed
Publication date: 2026/03/11
Ding Xiao-HongChen FenfangYang FanDi Gen-HongShao Zhi-MingXiao YiJiang Yi-Zhou - Treatment response in first-episode psychosis (FEP) is highly variable, and reliable biomarkers for poor outcomes remain limited. MicroRNAs (miRNAs), important post-transcriptional regulators, have been implicated in psychotic disorders. However, genome-wide miRNA profiling and analyses of their downstream gene networks related to treatment response in FEP remain insufficiently explored. - Source: PubMed
Publication date: 2026/02/04
Yu Shun-ChunWang Yun-ChuLin Hsiu-PingJen Ya-WenHwang Tzung-JengLiu Chih-MinChan Hung-YuKuo Chian-JueYang Tsung-TsairWang Jen-PangLiu Chen-ChungHsieh Ming HLin Yi-TingChien Yi-LingKuo Po-HsiuShih Ya-WenYu Sung-LiangChen Hsuan-YuWang CharlotteChen Wei J - Lipophagy, the selective autophagic degradation of lipid droplets (LDs), is a key mechanism for lipid homeostasis and cellular adaptation to metabolic and stress conditions. In mammals, lipophagy is governed by signaling pathways, LD-associated receptors (e.g. SQSTM1/p62, NBR1, OPTN, SPART, OSBPL8, DDHD2, VPS4A, ATG14, and TP53INP2), and transcription factors (TFEB, TFE3, FOXO1, PPARA, PPARG, and SREBF1/SREBP1) that coordinate LD recognition, sequestration, and lysosomal degradation. Dysregulated lipophagy contributes to the pathogenesis of metabolic and age-related diseases, including metabolic dysfunction-associated steatotic liver disease/nonalcoholic fatty liver disease (MASLD/NAFLD), alcoholic liver disease, diabetes, atherosclerosis, neurodegeneration and cancer. Several recent reviews have discussed lipophagy from different angles, including its roles in metabolic disorders, central nervous system diseases, and fundamental mechanisms across species. In contrast, this review focuses specifically on mammalian lipophagy by synthesizing the latest mechanistic insights into receptor-mediated recognition, transcriptional regulation, and signaling integration. We also outline unresolved questions and conceptual gaps - such as how lipophagy is selectively activated, how it coordinates with lipolysis, and whether distinct receptor codes exist in tissue- and disease-specific contexts - that remain unanswered in the current literature.: AMPK, AMP-activated protein kinase; ATG, autophagy related; ATG8s: mammalian Atg8-family proteins; C1P: ceramide-1-phosphate; CMA, chaperone-mediated autophagy; COPI, coatomer protein complex I; DENV, dengue virus; ER, endoplasmic reticulum; ESCRT: endosomal sorting complex required for transport; FFA: free fatty acid; HOPS, homotypic fusion and vacuole protein sorting; LDs, lipid droplets; LIR: LC3-interacting region; MASLD, metabolic dysfunction-associated steatotic liver disease; MTORC1: mechanistic target of rapamycin kinase complex 1; PE: phosphatidylethanolamine; PEDV: porcine epidemic diarrhea virus; PENV, porcine epidemic diarrhea virus; PtdIns3K-C1: class III phosphatidylinositol 3-kinase complex 1; PtdIns3P, phosphatidylinositol-3-phosphate; ROS, reactive oxygen species; SNARE: soluble NSF attachment protein receptor; SPG54: spastic paraplegia type 54; TAG: triacylglycerol/triglyceride; UBDs, ubiquitin-binding domains. - Source: PubMed
Publication date: 2026/02/18
Zhao RuiDai EnyongKang RuiLiu JiaoKlionsky Daniel JTang DaolinQu YangchunLin YuanqiangZhang Xinyue - Hereditary spastic paraplegia subtype SPG54 is a genetic neurological disorder caused by mutations in the DDHD2 gene. Excessive lipid droplet accumulation is observed in the brains of SPG54 patients and DDHD2 knockout mice, consistent with DDHD2's reported neutral lipase activity. Here, we find recombinant human DDHD2 preferentially hydrolyzes diacylglycerol (DAG) over phospholipids, with a slight preference for DAG over triacylglycerol (TAG). DDHD2 also exhibits transacylase activity, which enables transfer of acyl chains from TAGs to DAGs and monoacylglycerols to remodel the acyl chains of TAGs. A predicted hydrophobic amphipathic helix on DDHD2 is essential for lipid droplet binding in vitro and in cells, and its lack reduces the enzymatic activity and TAG acyl chain remodeling. Adipose triglyceride lipase, but not hormone sensitive lipase, also has transacylation activity and can remodel TAG acyl chains, but to a lesser extent than DDHD2. Taken together, this provides evidence that DDHD2 is a neutral lipid lipase and transacylase whose broad specificity enables TAG acyl-chain remodeling. - Source: PubMed
Publication date: 2025/11/20
Wu LingshuangChoi Yong MiOmrane MohyeddineChai JiyaoGao ShujuanThiam Abdou RachidCanals DanielAirola Michael V - Hereditary spastic paraplegia subtype SPG54 is a genetic neurological disorder caused by mutations in the DDHD2 gene. Excessive lipid droplet accumulation is observed in the brains of SPG54 patients and DDHD2 knockout mice, consistent with DDHD2's reported neutral lipase activity. Here, we find recombinant human DDHD2 preferentially hydrolyzes diacylglycerol (DAG) over phospholipids, with a slight preference for DAG over triacylglycerol (TAG). DDHD2 also exhibits transacylase activity, which enables transfer of acyl chains from triacylglycerols to diacylglycerols and monoacylglycerols to remodel the acyl chains of triglycerides. A predicted hydrophobic amphipathic helix on DDHD2 is essential for lipid droplet binding in vitro and in cells, and its lack reduces the enzymatic activity and triglyceride acyl chain remodeling. Adipose triglyceride lipase (ATGL), but not hormone sensitive lipase (HSL), also has transacylation activity and can remodel triglyceride acyl chains, but to a lesser extent than DDHD2. Taken together, this provides evidence that DDHD2 is a neutral lipid lipase and transacylase whose broad specificity enables triglyceride acyl-chain remodeling. - Source: PubMed
Publication date: 2025/09/22
Wu LingshuangChoi Yong MiOmrane MohyeddineChai JiyaoGao ShujuanThiam Abdou RachidCanals DanielAirola Michael V