The mouse Mcoln1 gene has two alternatively spliced isoforms, with isoform 2 having a different c-terminal cytoplasmic tail. The unique 86 amino acid c-terminal tail lacks the lysosomal targeting signal and does not contain any conserved domains when compared against the current profile databases. We speculate that this protein may have similar channel function but an alternate subcellular localization, but this must be proven once isoform-specific antibodies are raised. However, our results suggest that phenotypic assessment of Mcoln1 knock-out mice may be complicated and that care must be taken when interpreting data on mouse gene expression and phenotype.