SEH1L (SEH1 like nucleoporin) functions as a structural component of the GATOR2 complex, a nutrient-sensing hub that regulates mTORC1 signaling in response to amino acid availability 1. Within GATOR2, SEH1L, along with SEC13, stabilizes the complex's cage-like architecture through β-propeller blade donation, facilitating interactions with amino acid sensors SESN2 and CASTOR1 1. The GATOR2 complex activates mTORC1 by inhibiting GATOR1, and in amino acid-rich conditions, GATOR2 mediates ubiquitination of GATOR1 components, suppressing their activity 2. Conversely, amino acid deprivation inhibits GATOR2, allowing GATOR1 activation and mTORC1 suppression 3. Beyond mTOR regulation, SEH1L components interact with SUMO proteins through WD40 domains in an SIM-independent manner 4. Clinically, SEH1L upregulation correlates with poor prognosis across multiple cancers, and SEH1L knockdown suppresses hepatocellular carcinoma progression via ferroptosis induction through the ATF3/HMOX1/GPX4 axis 5. Additionally, SEH1L serves as a diagnostic biomarker for osteoarthritis, with reduced expression in OA patients and involvement in immune cell infiltration 67.