Genetic, colocalization, and biochemical studies suggest that the ankyrin repeat-containing proteins Inversin (INVS) and ANKS6 function with the NEK8 kinase to control tissue patterning and maintain organ physiology. It is unknown whether these three proteins assemble into a static “Inversin complex” or one that adopts multiple bioactive forms. Through characterization of hyperactive alleles in C. elegans, we discovered that the Inversin complex is activated by dimerization. Genome engineering of an RFP tag onto the nematode homologs of INVS (MLT-4) and NEK8 (NEKL-2) induced a gain-of-function, cyst-like phenotype called “jowls” that was suppressed by monomerization of the fluorescent tag. Stimulated dimerization of MLT-4 or NEKL-2 using optogenetics was sufficient to recapitulate the phenotype of a constitutively active Inversin complex. Further, dimerization of NEKL-2 bypassed a lethal MLT-4 mutant, demonstrating that the dimeric form is required for function. We propose that dynamic switching between at least two functionally distinct states—an active dimer and an inactive monomer—gates the output of the Inversin complex.Despite progress in understanding how the Inversin complex is activated, we lack an understanding of the downstream cell biology that the complex regulates. In C. elegans, the jowls phenotype caused by hyperactive Inversin complex mutants appears to be an aberrant detachment of the extracellular matrix, or the cuticle, from the epidermis, while loss of the complex results in inability to shed the cuticle. Thus, we tagged several structural constituents of the cuticle with GFP to monitor their organization and found that jowls-causing mutations disrupt multiple types of collagens that comprise the cuticle. As the C. elegans extracellular matrix is known to interact with the underlying cytoskeleton, we next generated a single copy insertion of a molecular probe for actin in order to assay the cytoskeletal structure, which revealed that the cytoskeleton is significantly disrupted in our jowls mutants. Together, these results suggest that the Inversin complex is activated by dimerization to regulate the organization of structural constituents of the cuticle as well as the underlying actin cytoskeleton.