Inactive phospholipase C-like protein 1

PLCL1 (inactive phospholipase C-like protein 1) is a 1,095-amino acid protein that participates in inositol phospholipid-based intracellular signaling, despite lacking canonical phospholipase C enzymatic activity toward its typical substrates (UniProt: Q15111). The protein functions in phospho-dependent endocytosis of GABA A receptors and regulates receptor turnover to maintain GABAergic synaptic inhibition. It also acts as an inhibitor of protein phosphatase 1C.

In the brain, PLCL1's role in GABAergic signaling positions it within inhibitory neurotransmission pathways critical for synaptic homeostasis. UniProt notes that aberrant expression could contribute to pathological processes, though no curated genetic disease associations are currently listed.

In Alzheimer's Disease, PLCL1 shows reduced abundance in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). The protein is significantly downregulated with a mean log2 fold-change of −0.692, based on TMT-labeled quantitative proteomics across subcellular fractions from human tissue. This downregulation may reflect impaired GABAergic signaling and altered receptor dynamics in the AD brain.