CANX (calnexin) is an endoplasmic reticulum (ER) transmembrane calcium-binding protein that functions as a critical regulator of protein quality control and cellular homeostasis. Mechanistically, CANX interacts with newly synthesized monoglucosylated glycoproteins in the ER lumen, facilitating protein folding and retention of misfolded proteins through the ER-associated degradation (ERAD) pathway 1. Beyond classical ER chaperone functions, CANX serves as a key node in autophagy regulation—it interacts with the autophagy-initiating kinase ULK1 and is required for ULK1 recruitment to the ER, thereby regulating autophagy flux under basal and nutrient-deprived conditions 2. CANX also regulates leucine-stimulated MTORC1 signaling through K525 crotonylation mediated by KAT7, with CANX translocating to lysosomes where it inhibits Ragulator activity 3. Disease relevance includes Alzheimer disease, where CANX-ULK1 interaction decline impairs autophagy and contributes to cognitive dysfunction; CANX overexpression in hippocampal neurons improves cognitive function in APP-PSEN1 mice 2. In glioblastoma, CANX overexpression promotes tumor progression through MEK/ERK/BNIP3-mediated protective mitophagy, and CANX knockdown combined with temozolomide extends survival 4. During HBV infection, CANX mediates cell-cell interactions between exhausted CD8+ T cells and regulatory CD4+ T cells through HLA class I molecules, contributing to immune dysfunction 5. Clinically, CANX represents a therapeutic target for enhancing chemotherapy sensitivity and improving autophagy-dependent disease outcomes.