HDAC4 (histone deacetylase 4) is a class IIa histone deacetylase that functions as a transcriptional corepressor through deacetylation of histones and non-histone proteins. HDAC4 regulates cellular processes through nuclear-cytoplasmic shuttling controlled by phosphorylation, with phosphorylated HDAC4 being excluded from the nucleus 1 2. The protein plays critical roles in muscle development and metabolism by interacting with MEF2 transcription factors, where nuclear export of HDAC4 leads to histone hyperacetylation on target gene promoters like GLUT4, enhancing their transcription 3. HDAC4 also regulates vascular processes, where its phosphorylation and nuclear exclusion promotes RUNX2 acetylation and nuclear translocation, contributing to vascular calcification 1. In cardiac tissue, HDAC4 can be cleaved by ABHD5 protease to generate an N-terminal fragment that inhibits MEF2-dependent gene expression and protects against heart failure 4. HDAC4 exhibits context-dependent effects on cellular senescence and autophagy regulation 5 2. Disease associations include neurodevelopmental disorders from HDAC4 haploinsufficiency 6 and potential oncogenic functions when constitutively nuclear 7. HDAC4 also cooperates with HDAC7 in regulating Th17 cell differentiation 8.