CKAP2L

Cilia effects upon perturbation of CKAP2L

Loss-of-function effect:

Longer cilia

Ciliogenesis screen results (3 screens)

• Wheway et al. 2015 (siRNA) [siRNA]: Ciliogenesis Defect (z=-5.16) PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Elliott et al. 2025 (CRISPRa) [CRISPRa]: Disassembly Trigger (casTLE Effect=-2.03) PMID:41160700

Phenotypes

Human ciliopathy phenotype:

Filippi syndrome (FLPIS, OMIM 272440): autosomal recessive craniodigital syndrome with pre- and postnatal growth retardation, microcephaly, distinctive facial appearance, syndactyly of fingers and toes, intellectual disability. CKAP2L localises to centrosome, mitotic spindle, and ciliary basal body; CKAP2L loss elongates primary cilia in human and mouse cells; Ckap2l KO mice show elongated sperm flagella (Hussain et al. 2014, PMID 25439729; Lyu et al. 2025, PMID 41370039).

Ciliopathy associations

• Filippi Syndrome

References: PMID:25439729, PMID:41370039, PMID:29397094, PMID:33913579

Subcellular localization

centrosome, cilia

References: PMID:41370039, PMID:41184298, PMID:41005307, PMID:42105234

Functional category

• Ciliary assembly/disassembly
• Actin & cytoskeleton regulation

Function

The reciprocal ciliary localization patterns of CKAP2L and DHX57 highlighting region-specific variations in ciliary composition between the dorsal and ventral brain regions., CKAP2L has localized in cilia (PMID 42105234). At the cellular level, CKAP2L is a bona fide microtubule-associated protein that localizes to microtubule-based organelles, including the centrosome, mitotic spindle, and ciliary basal body. Depletion of CKAP2L leads to shortened mitotic spindles and cytokinesis failure, resulting in multinucleation. Furthermore, we uncover a conserved function for CKAP2L as a negative regulator of primary cilium length; its loss markedly increases ciliary length in both human and mouse cells. (41370039) CKAP2L lies along the ciliary axoneme; Ckap2l knockout NIH3T3 cells have normal cilia length and ciliation rate but reduced Hedgehog signaling, with less SMO and GLI2 in cilia, and Ckap2l knockout mice have smaller brains and reduced cortical neurogenesis (PMID 42105234).