CCDC134 is an endoplasmic reticulum (ER)-resident molecular adapter that regulates protein glycosylation and chaperone function with critical roles in bone development and immune responses. Primary Function: CCDC134 prevents hyperglycosylation of HSP90B1 (Gp96), an ER chaperone essential for receptor trafficking 1. During HSP90B1 translocation, CCDC134 assembles a specialized translocon complex with the oligosaccharyltransferase OST-A, tethering the nascent chaperone to create a protective microenvironment 2. This prevents access to facultative glycosylation sites until folding completion, protecting HSP90B1 from degradation 1. Mechanism: CCDC134 controls TLR4 and other receptor biogenesis through gp96 stabilization 3. It recognizes a non-native conformation of nascent GRP94 via a hydrophobic groove, inhibiting OST-A activity 2. Loss of CCDC134 causes gp96 hyperglycosylation and ER-associated protein degradation, impairing TLR and WNT/IGF1R signaling 41. Disease Relevance: CCDC134 mutations cause osteogenesis imperfecta type XXII, a bone developmental disorder 15. CCDC134 downregulation promotes breast cancer cell migration via MAPK pathway activation 6. Expression is reduced in premature ovarian insufficiency, where overexpression restores ovarian function 7. Clinical Significance: CCDC134 represents a therapeutic target for bone disorders, cancer metastasis prevention, and ovarian reserve restoration.