2609076192ENSG00000100997ENSMUSG00000032046Q8N2K0Q99LR1NM_001042472NM_015600NM_024465NM_001356549NM_001356550NP_001035937NP_056415NP_077785NP_001343478NP_001343479alpha/beta-Hydrolase domain containing 12 (ABHD12) is a serine hydrolase encoded by the ABHD12 gene that participates in the breakdown of the endocannabinoid neurotransmitter 2-arachidonylglycerol (2-AG) in the central nervous system.

[6] ABHD12 is a ≈45 kDa integrated membrane glycoprotein, with an active site proposed to face into the extracellular space.

[9][5] ABHD12 transcription is abundant in the brain, specifically microglia, but has also been identified in peripheral cell types like macrophages and osteoclasts.

[14][18] In vitro, enzymatic activity of ABHD12 can be eliminated by site mutation the residues Serine-246, Aspartate-333, or Histidine-372, which form a catalytic triad in the hydrolase domain.

[6] The α/β hydrolase domain including lipase motif and catalytic triad is conserved between murine and human ABHD12.

[10] Mouse knockout (ABHD12 -/-) models demonstrate cerebellar microgliosis, motor and auditory impairment, alongside elevated neuroinflammation with progression associated with age.

[11] A zebrafish knockdown (+/-) model has been developed which demonstrates ophthalmic defects including microphthalmia, lack of lens clarity, and disrupted retina architecture.