GET4 (guided entry of tail-anchored proteins factor 4) functions as a core component of the BAG6/BAT3 cytosolic quality control complex that mediates post-translational protein targeting and quality control. As part of the transmembrane domain recognition (TRC) complex alongside BAG6 and UBL4A, GET4 facilitates delivery of tail-anchored proteins to the endoplasmic reticulum membrane 1. The complex coordinates with SGTA and ASNA1 to recognize hydrophobic transmembrane domains of newly synthesized proteins and load them onto the ATPase GET3 1. GET4 structurally primes GET3 for client loading by forming a composite lid over GET3's substrate-binding chamber 1. Beyond membrane protein targeting, GET4 participates in protein quality control by maintaining misfolded proteins in soluble states and directing them toward either ER delivery or proteasomal degradation 2. Nuclear BAG6-GET4-UBL4A complexes also mediate DNA damage signaling, with GET4 translocating to the nucleus upon DNA damage to facilitate cell death responses 3. Clinically, GET4 mutations cause congenital disorder of glycosylation 2Y, presenting with developmental delay, intellectual disability, and seizures due to disrupted tail-anchored protein targeting and retrograde ER-Golgi transport 2. GET4 is amplified and overexpressed in colorectal cancer, promoting tumor progression through enhanced BAG6 cytoplasmic localization and p53 acetylation 4. Additionally, GET4 emerges as an endoplasmic reticulum stress-related biomarker for type 1 diabetic cardiomyopathy 5.