MS4A8B regulates Orai1-dependent Ca²⁺ influx to control motile cilia function in human nasal epithelial cells

The primary cilium as a compartmentalized signaling hub in tissue immunity and homeostasis

Cilia are evolutionarily conserved microtubule-based organelles that function as sensory and motile hubs central to mucosal immunity and systemic immune homeostasis. Motile cilia drive mucociliary clearance as a primary physical defense; meanwhile primary cilia function as signaling scaffolds that regulate immune receptor dynamics including PD-L1 trafficking. These organelles also modulate inflammatory responses through pathways such as cGAS-STING. Disruptions in ciliary assembly, intraflagellar transport, or signaling drive pathological immune dysregulation, contributing to viral infections, chronic inflammatory diseases, and ciliopathy-related immune dysfunction. This review summarizes core ciliary signaling pathways and their roles in host defense and immune homeostasis, integrating recent advances linking ciliary defects to diverse immune-related pathologies. We discuss current limitations in understanding ciliary immunobiology and propose key directions for future research aimed at deepening mechanistic insights and facilitating clinical translation.

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Transcriptomics of independent CRISPR-edited cell lines reveal ciliary-specific ARL13B dependent changes

It is demonstrated that ciliary ARL13B is required to maintain normal ciliary composition and gene expression programs and underscores the value of multi-clone, rescue-based experimental designs for robust transcriptomic analyses.

Lipid ciliology: specialized ciliary membrane lipids in physiology and disease

Primary cilia are the microtubule-based sensory organelles. The unique lipid makeup of the ciliary membrane strictly controls their signaling ability, to orchestrate tissue formation and homeostasis. Emerging evidence has demonstrated that lipids play important roles in cilia formation and cilia-related signaling, solidifying the previously proposed concept of “lipid ciliology.” The ciliary membrane exhibits a highly specialized lipid composition, including enrichment in cholesterol, sphingolipids, and specific phosphoinositides, compared with the surrounding plasma membrane. Recent studies have revealed that cholesterol and phosphoinositides function together to regulate ciliary homeostasis, protein trafficking, and signal transduction. A growing spectrum of ciliopathies, including polycystic kidney disease, retinal degeneration, cerebellar hypoplasia, and metabolic disorders, can be caused by dysregulation of lipid metabolism and lipid-modifying enzymes through impaired cilia-related signaling. Moreover, defects in cholesterol biosynthesis or intracellular lipid transport contribute to various ciliopathies, such as Smith–Lemli–Opitz syndrome and Zellweger spectrum disorders. In this review, we summarize recent advances in lipid ciliology, focusing on the underlying molecular mechanisms of ciliary cholesterol-dependent signaling in ciliopathies for emerging therapeutic strategies.

3D nanoscale reconstruction of human airway multiciliogenesis reveals cellular architecture remodeling and cilia-mitochondria link via rootlets.

A central challenge in single-cell biology is understanding how molecular programs drive changes in cellular architecture that enable specialized function. A striking example of cellular remodeling is the differentiation of airway stem cells into the respiratory multiciliated epithelium, a protective tissue barrier that clears inhaled pathogens and particulate matter. Here, we present its first three-dimensional nanometer-scale reconstruction, revealing coordinated changes in cellular organization, organelle topology, and inter-organelle contacts during multiciliogenesis. We uncover a structural and functional association between motile cilia and mitochondria mediated by rootlets, striated cytoskeletal fibers that remain poorly characterized in human airway multiciliated cells. Rootlets connect to basal bodies through a multiprotein linker containing the uncharacterized rootletin/CROCC homolog CROCC2, oscillate at frequencies comparable to ciliary beating, promote basal body alignment, and when lost, reduce maximal mitochondrial respiratory capacity. Altogether, this work integrates structural, dynamic, and functional analyses to elucidate mechanisms underlying airway mucociliary defense.

Regulation of de- and reciliation by KRAS during muscle cell differentiation

A major mediator of mitogenic signaling into the regulation of ciliogenesis of proliferating muscle stem- and progenitor cells is integrated into the regulation of ciliogenesis of proliferating muscle stem- and progenitor cells.