GABAA receptor-associated protein-like 1 (GABARAPL1) is a protein encoded by the GABARAPL1 gene in humans and is a member of the GABARAP family of proteins. It contains a ubiquitin-like core of β-sheets and α-helices, with two additional α-helices at the N-terminus. The GABARAPL1 gene is expressed in a variety of tissues, including the brain, heart, liver, kidney, and placenta, among others, and the protein is highly expressed in the brain and the lungs. GABARAPL1 interacts with tubulin and the γ2 subunit of the GABAA receptor and promotes tubulin polymerization and microtubule formation. It also interacts with the κ-opioid receptor to increase receptor expression in the plasma membrane. GABARAPL1 is involved in autophagy where it interacts with the autophagy cargo adaptor proteins p62 and NBR1 to facilitate degradation of ubiquitinated protein aggregates. The GABARAPL1 gene contains potential estrogen regulatory elements, and GABARAPL1 expression is higher in breast adenocarcinoma tumors from lymph node-positive patients that had a lower risk of metastasis. However, GABARAPL1 expression is upregulated in patient-derived triple negative breast cancer (TNBC) tissue and inhibition of its activity in an MDA-MB-231 mouse xenograft model suppresses cell proliferation, tumorigenesis, and metastasis.
