Human podocin and C. elegans MEC-2 belong to the stomatin protein superfamily. They share 49% identity and 91% similarity both in the evolutionary conserved PHB domain (123-284 aa) and in the oligomerization region (273-351 aa). Amino acid substitutions in these conserved regions can modify the podocin oligomerization and thus the pathogenicity of trans-associated NPHS2 variants, known as interallelic interactions. The MEC-2A isoform was formerly considered to be the functional isoform and used to evaluate the effect of pathogenic podocin variants. The mec-2 mutant worms are mechanosensation deficient, and, as recently described, also chemosensation deficient. To study the interallelic interactions of podocin in vivo, we aimed to rescue the phenotype of the mec-2 mutant worm by reexpressing podocin (383 aa). However, we did not detect any chemotaxis defects in mec-2(u37) null mutants nor in mec-2(e75) missense mutants. No mechanosensation rescue was achieved by MEC-2A, but with a 17,5 kb genomic region and the MEC-2E isoform (1239 aa) with a large C-terminal. Truncating the last third of the large C-terminal abolished its rescue effect. In conclusion, the function of MEC-2 in mechanosensation requires a large C-terminal encoded by the MEC-2E isoform. Accordingly, human podocin cannot rescue the phenotype of mec-2 mutants.