TMEM106A (transmembrane protein 106A) is a plasma membrane and mitochondrial protein that functions primarily as a macrophage activator and tumor suppressor. In macrophages, TMEM106A activation triggers M1-like polarization through MAPK and NF-κB signaling pathways 1, upregulating surface markers CD80, CD86, CD69, and MHC II while inducing pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, CCL2, and nitric oxide 1. In disease contexts, TMEM106A demonstrates opposing roles: it promotes atherosclerosis progression by enhancing macrophage infiltration, foam cell formation, and inflammatory responses through chemokine signaling regulation 2, while functioning as a tumor suppressor in multiple cancers. In non-small-cell lung carcinoma, gastric cancer, and hepatocellular carcinoma, TMEM106A overexpression inhibits cell proliferation, migration, invasion, and induces apoptosis by suppressing epithelial-mesenchymal transition through PI3K/Akt/NF-κB and Erk1/2/Slug pathway inactivation 345. TMEM106A expression is frequently silenced by promoter hypermethylation in cancers, correlating with poor prognosis 45. Recent evidence links TMEM106A to genetic generalized epilepsy pathogenesis through immune-related mechanisms 6. These findings position TMEM106A as a clinically relevant biomarker with therapeutic potential in both inflammatory and neoplastic diseases.