Abhydrolase domain-containing protein 17 (ABHD17)

Abhydrolase domain-containing protein 17 (ABHD17) is a family of serine hydrolases, including isoforms ABHD17A, ABHD17B, and ABHD17C, that function as the primary protein depalmitoylases in mammalian cells (Lin & Conibear, 2015, Nature Chemical Biology). These enzymes are responsible for removing palmitate from cysteine residues, a reversible post-translational modification that regulates the membrane association and signaling of various proteins (Remsberg et al., 2021, Nature Chemical Biology). ABHD17 is particularly critical for the dynamic regulation of the postsynaptic density protein PSD-95, which is essential for maintaining synaptic plasticity and strength (Yokoi et al., 2016, Journal of Neuroscience). Additionally, ABHD17 has been identified as a key regulator of the N-Ras oncogene, controlling its localization and oncogenic signaling (Lin & Conibear, 2015). Because of its central role in these pathways, ABHD17 is considered a promising therapeutic target for neurodegenerative diseases and certain types of cancer. Small-molecule inhibitors, such as ABX-1772, have been developed to selectively inhibit ABHD17 activity, allowing researchers to study the effects of stabilized palmitoylation on target proteins (Remsberg et al., 2021). These inhibitors represent a potential therapeutic strategy for restoring synaptic function or dampening oncogenic signaling.

Other names

Alpha/beta hydrolase domain-containing protein 17FAM108Protein depalmitoylase ABHD17

Inhibition of the depalmitoylase activity of ABHD17 to maintain the palmitoylated (membrane-bound) state of substrate proteins like PSD-95 or N-Ras.