Primary cilia function as hubs for signal transduction

Primary cilia are solitary, non-motile, microtubule-based organelles that protrude from the surface of most vertebrate cells, functioning as highly specialized sensory and signaling compartments. Architecturally, they comprise the basal body, transition zone, and 9 + 0 axoneme, which together establish a biochemically distinct and selectively permeable domain, spatially segregated from the cytoplasm. This compartmentalization enables primary cilia to integrate and modulate diverse signaling cascades, including Hedgehog, Wnt, Notch, TGF-β/BMP, Hippo, cGAS-STING, calcium, GPCR, and phosphoinositide cascades, thereby coordinating developmental programs, tissue patterning, and homeostatic regulation. Ciliogenesis proceeds through basal body docking to the plasma membrane, vesicle fusion, and axoneme elongation, a sequence precisely orchestrated by bidirectional trafficking machinery of intraflagellar transport (IFT). The dynamic equilibrium between ciliary assembly and disassembly is closely coupled to cell cycle progression and signaling flux. Within the confined ciliary compartment, molecular gating at the transition zone and the polarized trafficking of receptors and effectors confer stringent control over pathway specificity and signal fidelity. Disruption of primary cilia perturbs this spatiotemporal precision, resulting in defective signal integration and a broad spectrum of disorders collectively termed ciliopathies, which range from congenital malformations to metabolic and neoplastic diseases. This review summarizes recent advances in elucidating the structural architecture, biogenesis, and signaling functions of primary cilia, highlighting their critical roles in vertebrate biology and disease.