Primary cilium as a sensory organelle and metabolic hub in health and diseases

Abstract

Primary cilia are microtubule-based organelles protruding from the cell surface, which are conventionally understood as passive cellular antennae that detect extracellular stimuli. However, emerging evidence redefines these microtubule-based organelles as dynamic, bidirectional hubs that integrate environmental sensing with cellular metabolic adaptation. By selectively compartmentalizing receptors, ion channels, transporters, and signaling components, they function as specialized signal-processing compartments that receive, integrate, amplify, and relay information to coordinate cellular metabolism, adaptation, and cell-fate determination. Cilia-dependent signaling pathways regulate glucose and lipid metabolism, Ca2⁺ and second-messenger dynamics, and mitochondrial homeostasis. Conversely, environmental and metabolic changes remodel ciliary structure, molecular composition, and signaling competence. In this review, we present primary cilia as a bidirectional interface between environmental sensing and metabolic adaptation. We discuss how cilia respond to nutrient availability, mechanical forces, and oxygen tension, and how disruption of this sensory-metabolic interface contributes to metabolic, cardiovascular, reproductive, neurodegenerative, and cancer-related diseases. Defining the cellular and environmental contexts in which ciliary remodeling is protective or pathogenic will be essential for translating cilia biology into therapeutic strategies.