GET3 is an ATPase that functions as the central component of the GET (guided entry of tail-anchored proteins) pathway, mediating post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum 1. GET3 recognizes and selectively binds the transmembrane domain of nascent TA proteins in the cytosol through a hydrophobic groove 2. The protein operates through a nucleotide-dependent cycle: ATP binding drives GET3 toward a closed conformation facilitating TA protein recognition, while ATP hydrolysis enables transfer of the substrate to the membrane-bound GET1/CAMLG receptor complex 3. Following insertion, GET3 reverts to its open conformation, lowering receptor affinity and allowing cytosolic recycling 4. The GET1/Get2 insertase forms an aqueous channel approximately 2.5 nm in diameter that mediates TMD insertion into the lipid bilayer, with GET3 binding capable of sealing this channel 5. GET3 also exhibits chaperone holdase activity independent of its targeting function 2. Clinically, mutations in GET3 cause dilated cardiomyopathy 2H 6, while defects in the GET pathway components, including GET4, cause congenital disorders of glycosylation with neurological manifestations, highlighting GET3's importance in protein biogenesis and organellar function.