CDKN2A and neoplasm: Butyrate and other short-chain fatty acids (SCFAs) act as endogenous class I/IIa HDACi; their depletion removes a physiological brake on HDAC activity, thereby favoring re-establishment of repressive chromatin and promoter hypermethylation at tumor-suppressor loci (e.g., CDKN2A) in aging urothelium (Schilderink et al., 2013; Borrego-Ruiz and Borrego, 2024; Chen et al., 2023a).