SH3GL1 encodes endophilin A2, a membrane-associated protein that plays crucial roles in endocytosis and cellular signaling across multiple biological contexts. The protein functions as a key regulator of membrane dynamics, facilitating endocytosis and protein recycling processes 1. In immune regulation, SH3GL1 modulates T cell activation thresholds and affects T cell receptor internalization, with deficiency providing protection from autoimmune arthritis in rodent models 2. The protein also regulates B cell responses, as endophilin A2 deficiency impairs antibody production and switched memory B cell development in humans 3. In cancer biology, SH3GL1 demonstrates oncogenic properties through multiple mechanisms: it promotes cell survival by inhibiting ferroptosis via FTH1 regulation in diffuse large B-cell lymphoma 4, facilitates immune escape by enhancing B7-H3 recycling in non-small cell lung cancer 1, and drives osteosarcoma progression through P130cas phosphorylation and Akt/GSK-3β/FAK signaling pathways 5. The protein serves as a biomarker, with elevated expression correlating with poor prognosis in various cancers and eliciting autoantibody responses specifically in low-grade gliomas 6. These diverse functions establish SH3GL1 as a critical regulator of membrane trafficking, immune responses, and cellular survival mechanisms.