Primary cilia: master conductors of cellular communication in development and disease

Primary cilia are microtubule-based organelles that function as cellular antennae, integrating diverse signalling pathways essential for tissue development and function. Dysregulation of ciliary signalling is linked to a broad spectrum of disorders known as ciliopathies, which affect most tissues and organs in the body. Primary cilia are dynamic hubs in which selective trafficking and compartmentalization of receptors, effectors and second messengers shape the strength, duration and specificity of cellular responses. Intraflagellar transport, ciliary gating and cargo adaptors establish and dynamically remodel ciliary composition, enabling signalling through Hedgehog, G-protein-coupled receptors, transient receptor potential proteins, receptor tyrosine kinases and the TGFβ superfamily to coordinate developmental patterning, cell proliferation and differentiation, metabolism and tissue homeostasis. Disruption of ciliary architecture, trafficking or signalling can therefore produce diverse and tissue-specific disease phenotypes, including polycystic kidney disease, retinal degeneration, skeletal abnormalities, cardiovascular diseases, neurodevelopmental disorders and obesity. Emerging evidence indicates that cell-type-specific and temporally dynamic ciliary signatures determine signalling competence and disease susceptibility. Defining these signatures and the mechanisms that regulate their plasticity could lead to new therapeutic opportunities for ciliopathies and other cilia-associated diseases.