Abstract

Eukaryotic cells interact with their environment through the secretory pathway, which involves the endoplasmic reticulum (ER), Golgi complex (GC), and endolysosomal system. These organelles regulate protein folding, post-translational modifications, and trafficking of structural and signaling proteins essential for cellular homeostasis. The KDEL receptor (KDELR), a cargo and signaling receptor located in the Golgi complex (GC), plays a crucial role in maintaining the balance of the secretory pathway by sensing cargo arrival from the endoplasmic reticulum (ER) and activating signaling pathways. Dysfunction in this pathway contributes to diseases such as diabetes, neurodegenerative disorders, and cancer. Recent studies highlight KDELR's involvement in cancer progression, yet its precise role remains unclear. This review provides an overview of KDELR's structure and function, highlighting its emerging significance in cancer biology. © 2025 Elsevier B.V.