Fibrotic diseases are characterized by persistent extracellular matrix (ECM) remodeling and excessive accumulation of fibrillar collagens, particularly Type I collagen (Col I), which collectively drive tissue stiffening, architectural distortion, and progressive organ dysfunction. However, pathological Col I dysregulation is not limited to overproduction or deposition; it may also involve defective folding, impaired trafficking, abnormal secretion, insufficient degradation, or altered collagen availability in specific disease contexts. Emerging evidence identifies autophagy as a central regulator of this network. Beyond its canonical degradative function, autophagy integrates procollagen quality control, endoplasmic reticulum (ER) stress adaptation, selective ER-phagy, and lysosome-dependent collagen turnover. Among these processes, selective ER-phagy eliminates misfolded or surplus procollagen, whereas secretory autophagy and lysosomal turnover determine whether collagen is exported, retained, or degraded. In fibrotic disease, impaired ER-phagy, maladaptive secretory autophagy, and defective lysosomal flux collectively promote ER stress, aberrant collagen secretion, ECM accumulation, and matrix stiffening. This review summarizes current understanding of the autophagy-Col I axis across the collagen lifecycle, discusses how its dysregulation contributes to fibrotic remodeling, and highlights checkpoint-focused therapeutic strategies aimed at restoring collagen clearance and ECM homeostasis.
