MTUS1 (microtubule-associated scaffold protein 1) is a tumor suppressor gene located at chromosome 8 that encodes a family of proteins (ATIP isoforms) with distinct subcellular localizations and functions 1. The gene produces multiple isoforms with different tissue distributions: ATIP1 is ubiquitous and brain-enriched, ATIP3 is predominant in cancer-prone tissues (prostate, bladder, breast, ovary, colon), and ATIP4 is brain-specific 1. Mechanistically, MTUS1 inhibits cell proliferation through multiple pathways. ATIP1 localizes to the outer mitochondrial membrane where it interacts with MFN2, stimulates reactive oxygen species (ROS) production, and induces GSDME-dependent pyroptotic cell death in head and neck squamous cell carcinoma 2. The mitochondrial isoform Mtus1A functions as a scaffold protein maintaining the IP3R1-Grp75-VDAC1 complex at mitochondria-associated ER membranes (MAMs), preserving ER-mitochondria communication and mitochondrial function 3. Downregulation of MTUS1 is frequently observed in multiple human cancers including pancreatic, colorectal, bladder, head-and-neck, ovarian, breast, gastric, and lung cancers 4. In colorectal cancer, low MTUS1 expression correlates with poor overall survival and serves as an independent prognostic factor 5. Beyond cancer, mutations in MTUS1 occur in hepatocellular carcinoma 6, and reduced expression is associated with cardiac dysfunction after myocardial infarction 3. MTUS1 also appears protective in mesothelioma 7.