TMBIM1 (transmembrane BAX inhibitor motif containing 1) is a multifunctional regulator of cellular degradation pathways with broad disease relevance. Mechanistically, TMBIM1 functions as a multivesicular body (MVB) regulator that promotes lysosomal degradation of key signaling proteins, particularly toll-like receptor 4 (TLR4) 12. TMBIM1 interacts with tumor susceptibility gene 101 via a PTAP motif to facilitate MVB formation and subsequent lysosomal delivery 2. Beyond lysosomal pathways, TMBIM1 regulates autophagy and mitophagy; it promotes autophagic degradation of E-cadherin in glioblastoma 3 and facilitates Parkin-mediated mitophagy during sepsis-induced cardiac dysfunction 4. In cancer contexts, TMBIM1 demonstrates pleiotropic effects. It is upregulated in pancreatic cancer, where it orchestrates an immunosuppressive microenvironment through a TMBIM1-YBX1 axis that increases PD-L1 and CCL2 expression, promoting MDSC infiltration 5. A genome-wide association study identified TMBIM1 as part of a colorectal cancer risk locus (rs992157) showing pleiotropy with inflammatory bowel disease 6, with epigenetic analysis revealing methylation changes at TMBIM1-proximal CpG sites associate with air pollution-related CRC risk 7. In non-malignant disease, TMBIM1 is protective: overexpression inhibits NAFLD progression and steatohepatitis through TLR4 degradation 1, alleviates pathological cardiac hypertrophy 2, and reduces sepsis-induced cardiac dysfunction 4. miR-582-3p-mediated TMBIM1 suppression ameliorates NASH 8.