MEF2C is a transcription factor with critical roles across multiple biological systems. In cardiac development, MEF2C controls segment-specific gene regulatory networks essential for heart tube morphogenesis, with loss of function resulting in cardiac malformations partly driven by aberrant NR2F2 activity 1. MEF2C also functions as a master regulator of heart valve cell differentiation, acting as a key switch gene during endocardial-mesenchymal transition 2. Beyond cardiac tissue, MEF2C serves as a crucial immune checkpoint maintaining microglial homeostasis through the MEF2C-p21-CDK2-RB-NFκB axis, preventing pathological microglial overactivation implicated in autism spectrum disorder 3. MEF2C loss in human microglia induces hyperinflammation, phagocytic impairment, and lipid accumulation, with substantial overlap to idiopathic autism pathology 4. Additionally, MEF2C regulates natural killer cell effector functions by controlling lipid metabolism through sterol regulatory element-binding protein pathways, and MEF2C-haploinsufficient patients exhibit defective NK cell development and increased viral susceptibility 5. In cancer immunology, MEF2C maintains VSIG4 expression in tumor-associated macrophages, promoting immunosuppression that can be therapeutically targeted 6. In meningioma, MEF2C transcriptionally drives NF2 and E-cadherin expression, controlling ferroptosis susceptibility 7. Clinically, MEF2C haploinsufficiency causes severe neurodevelopmental disorder characterized by intellectual disability, refractory epilepsy, stereotypic movements, and brain abnormalities 8.