Autophagy and primary cilium: A dynamic duo in cellular homeostasis and disease

The primary cilium (PC) is a microtubule-based organelle that functions as a signaling hub, coordinating critical cellular processes and maintaining cell homeostasis. Autophagy, a lysosome-mediated degradation pathway, has emerged as a key regulator of PC dynamics, which are crucial to control PC function. Ciliophagy, the selective autophagic degradation of damaged ciliary components, controls PC homeostasis ensuring PC integrity and function. This review highlights the intricate bidirectional crosstalk between the PC and autophagy, which influences cellular responses to environmental cues, nutrient availability, and hormonal signaling. Disruption of ciliophagy impairs PC-dependent signaling, contributing to the development of diseases such as ciliopathies and metabolic syndrome, among others. Furthermore, the overlap between ciliopathies and autophagy-related disorders underscores the crucial role of their interplay in health and disease. Recent evidence suggests that pharmacological modulation of autophagy could restore PC homeostasis, offering therapeutic potential for ciliopathies and other PC-associated diseases. Future research should focus on elucidating the molecular mechanisms driving ciliophagy in specific cell-types and exploring its therapeutic implications for clinical applications.