STOML2 is a mitochondrial inner membrane protein that regulates mitochondrial biogenesis and function through multiple interconnected pathways. Primary function: STOML2 stimulates cardiolipin biosynthesis, binds cardiolipin-enriched membranes, and recruits stabilizing proteins including prohibitin to organize functional microdomains 1. Mechanism: STOML2 operates through two major signaling axes. In cancer contexts, it interacts with and stabilizes PINK1 to amplify PINK1-Parkin-mediated mitophagy, promoting HCC metastasis 2, while paradoxically restricting mitophagy in pancreatic cancer by stabilizing PARL-induced PINK1 degradation to enhance chemosensitivity 3. STOML2 also activates MEK/ERK and NF-κB signaling through PHB interaction, promoting proliferation and tumor-supporting immune escape 45. Disease relevance: STOML2 is upregulated in multiple solid tumors and associated with poor prognosis, metastasis, and chemoresistance 25. Additionally, STOML2 expression correlates with asthma risk through IL-6 signaling modulation and T-cell activation 6. Clinical significance: STOML2 represents a dual therapeutic opportunity—as a biomarker for patient stratification and as a therapeutic target, with potential benefits from combined mitophagy and angiogenesis inhibition in HCC or MAPK pathway blockade in other malignancies 25.