ABHD14B is an atypical protein-lysine deacetylase that catalyzes the deacetylation of acetylated lysine residues using coenzyme A as substrate, generating acetyl-CoA and free protein lysine 1. The enzyme also possesses hydrolase activity toward various p-nitrophenyl substrates with preference for p-nitrophenyl acetate 1. While biochemical evidence demonstrates these activities in vitro, confirmation of protein-lysine deacetylase activity in vivo remains pending 1. Clinically, ABHD14B functions as a host factor regulating hepatitis B virus cccDNA transcription by interacting with cccDNA-associated proteins and reducing histone acetylation levels, thereby suppressing HBV RNA transcription 2. ABHD14B has been identified as a candidate therapeutic target in gout through multi-omics Mendelian randomization analysis 3 and shows protective associations with breast cancer mortality, with high tumor expression correlating with improved survival 4. Additionally, ABHD14B has been identified as one of five key proteins distinguishing parathyroid carcinoma from adenoma 5 and as a protective biomarker for rosacea development 6. Emerging evidence suggests ABHD14B's role in cellular regulation extends to DNA methylation and developmental processes 7. These findings establish ABHD14B as a multifunctional enzyme with relevance across viral infection, malignancy, and inflammatory disease contexts.