AP1M2 (adaptor related protein complex 1 subunit mu 2) is the medium chain subunit of the clathrin-associated AP-1 complex located on chromosome 19.2 1. As a core component of the AP-1 adaptor complex, AP1M2 mediates protein sorting at the trans-Golgi network (TGN) and endosomes by facilitating clathrin recruitment to membranes and recognizing cargo sorting signals 2. AP1M2 is essential for proper vesicle-mediated transport and polarized secretion in epithelial cells. Beyond canonical trafficking functions, AP1M2 plays critical regulatory roles in disease pathogenesis. AP1M2 deficiency causes autoinflammatory disease with colitis through impaired suppression of NF-κB activation; accumulation of TNFR1-signaling proteins (RIPK1, TBK1, IKKα/β, NEMO) leads to excessive chemokine production 3. Conversely, AP1M2 upregulation drives chemoresistance in bladder cancer by stabilizing RAD54B mRNA through interaction with RNA-binding protein PUM1, enhancing DNA repair capacity 4. AP1M2 also promotes triple-negative breast cancer progression and docetaxel resistance via PBX1-mediated transcriptional activation 5, and hepatocellular carcinoma growth through JNK/ERK pathway activation 6. Multi-omics studies identify AP1M2 as causally linked to non-obstructive azoospermia when influenced by environmental endocrine-disrupting chemicals 7.