RETREG3 (reticulophagy regulator family member 3), also known as FAM134C, is an endoplasmic reticulum (ER)-anchored autophagy receptor that exists in an inactive state under basal conditions but is activated following cellular stress 1. Upon activation, RETREG3 induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins 1. The protein promotes ER membrane curvature and tubulation required for ER fragmentation and autophagosome engulfment 2. RETREG3 function depends critically on its LC3-interacting region (LIR) motif 13. Beyond canonical ER-phagy, RETREG3 functions as a selective autophagy receptor for type I BMP receptors (BMPR1A), recruiting them into LC3-containing autophagosomes for degradation, thereby restraining BMP signaling 3. RETREG3 activity is regulated by phosphorylation-dependent ubiquitination mediated by casein kinase 2 (CSNK2/CK2), a process prerequisite for formation of high-density receptor clusters and reticulophagy flux 4. In vivo, RETREG3-deficient mice exhibit enhanced BMP responses in intestinal tissue, affecting intestinal crypt regeneration 3. These findings establish RETREG3 as a multifunctional regulator controlling both ER homeostasis and specific signaling pathways through selective autophagy.