CLVS1 (clavesin 1) is a neuron-specific Sec14 domain-containing protein that regulates late endosome and lysosome morphology 1. The protein localizes to clathrin-coated vesicles (CCVs) at the trans-Golgi network and forms complexes with clathrin heavy chain and adaptor protein-1 1. CLVS1 binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a lipid marker of late endosomes/lysosomes, through its Sec14 domain 1. Knockdown of CLVS1 in neurons causes enlargement of lysosomal compartments, indicating its critical role in endosomal-lysosomal dynamics 1. CLVS1 dysfunction has significant clinical relevance. A homozygous segregating variant (p.H310Y) was identified in familial steroid-sensitive nephrotic syndrome (SSNS) patients and caused podocyte dysfunction through impaired clathrin-mediated endocytosis and increased oxidative stress 2. The variant disrupted CLVS1 binding to α-tocopherol transfer protein, leading to reactive oxygen species accumulation; corticosteroid treatment rescued these deficits 2. Additionally, CLVS1 was identified as a component in an autophagy-related gene signature for clear cell renal cell carcinoma prognosis 3, and was associated with suicidal ideation in schizophrenia patients, potentially through lysosomal maturation dysfunction 4.