STON1 (stonin 1) is an endocytic adapter protein involved in regulating clathrin-dependent endocytosis and synaptic vesicle dynamics. Structurally, STON1 contains a proline-rich domain and a region homologous to AP complex mu subunits, characteristic of endocytic machinery components 1. While stonin 2 directly interacts with Eps15 and intersectin proteins, STON1's specific endocytic interactions remain less characterized 1. Beyond its canonical endocytic role, STON1 has emerged as a disease-associated locus through genome-wide association studies. STON1 variants associate with polycystic ovary syndrome (PCOS) pathogenesis, where STON1 is upregulated and co-expresses with genes involved in adipocyte metabolism 2. STON1 also influences AMD bilaterality risk 3 and associates with immunotherapy response in non-small cell lung cancer via effects on mismatch repair and immune regulation 4. In kidney renal clear cell carcinoma, decreased STON1 expression correlates with poor prognosis and correlates with tumor immune microenvironment composition, predicting favorable immunotherapy response but poor targeted treatment outcomes 5. Additionally, STON1 exhibits differential DNA methylation associated with FTO obesity risk alleles 6. These findings suggest STON1 functions at the intersection of endocytic regulation and metabolic-immune homeostasis, with clinical relevance for multiple diseases.