ABHD17

ABHD17 refers to a small family of human serine hydrolases encoded by the ABHD17A, ABHD17B, and ABHD17C genes. They belong to the alpha/beta hydrolase domain-containing (ABHD) superfamily and share the catalytic features of serine hydrolases, including a conserved catalytic triad and structural fold typical of this enzyme class.

Biological role: ABHD17A, ABHD17B, and ABHD17C function as depalmitoylases, removing palmitoyl groups from S-palmitoylated proteins. This depalmitoylation cycle counterbalances the action of ZDHHC palmitoyltransferases and regulates protein trafficking, localization, and signaling. In cells, ABHD17 activity can influence the membrane association and subcellular distribution of substrates such as the postsynaptic scaffolding protein PSD-95 and certain small GTPases, among others.

Localization and expression: ABHD17 proteins are primarily cytosolic but can associate with membranes when acting on palmitoylated substrates. Expression of the ABHD17 genes is broad across tissues but shows notable enrichment in the nervous system, where they are implicated in synaptic function and neuronal development.

Structure and enzymology: Each ABHD17 member contains the alpha/beta hydrolase catalytic core and demonstrates serine hydrolase activity in biochemical assays. While a core substrate class is established, the full range of physiological substrates and regulatory mechanisms is still being defined, with tissue- and context-dependent differences reported in the literature.

Clinical and research context: Because depalmitoylation modulates protein localization and signaling, ABHD17 proteins are studied for roles in neural function and disease. There are no approved therapies targeting ABHD17, and ongoing research aims to map substrate spectra, regulatory controls, and physiological pathways involving these enzymes.