Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific, growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development, but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth, survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. Plays a critical role in the regulation of neuronal apoptosis (By similarity). Interacts with MYOG (By similarity). Forms a complex with class II HDACs in undifferentiating cells. On myogenic differentiation, HDACs are released into the cytoplasm allowing MEF2s to interact with other proteins for activation. Interacts with HDAC4 (in undifferentiating cells); the interaction translocates MEF2D to nuclear dots. Forms a heterodimer with MEF2A. Interacts with MAPK7; the interaction phosphorylates but does not activate MEF2D (By similarity). Interacts with CCAR2 and HDAC3. Translocated by HDAC4 to nuclear dots. Present in myotubes and also in undifferentiated myoblasts. The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity. Phosphorylated on Ser-444 by CDK5 is required for Lys-439 sumoylation and inhibits transcriptional activity. In neurons, enhanced CDK5 activity induced by neurotoxins promotes caspase 3-mediated cleavage leading to neuron apoptosis. Phosphorylation on Ser-180 can be enhanced by EGF. Phosphorylated and activated by CaMK4. Acetylated on Lys-439 by CREBBP. Acetylated by EP300. Deacetylated by SIRT1 and HDAC3. Sumoylated on Lys-439 with SUMO2 but not SUMO1; which inhibits transcriptional activity and myogenic activity. Desumoylated by SENP3. Proteolytically cleaved in cerebellar granule neurons on several sites by caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation (By similarity). Belongs to the MEF2 family.