Cryptic Last Exons (CLEs) are unannotated terminal exons embedded in introns and their inclusion results in shorter mRNA that can be translated into truncated proteins. CLE-mRNAs were predominantly described in neurodegenerative disease, where they are widely interpreted as pathological and consequence of splicing dysfunction. Whether CLE-mRNAs are expressed under physiological conditions or contribute to normal gene regulation remained unknown. Here, we show that CLEs are used in normal cellular events. Large scale analysis of public RNA sequencing datasets revealed thousands of CLE mRNAs in wild-type tissues. While CLE sequences were not conserved, CLE usage repeatedly occurred in homologous genes across species. This indicates a selection for CLE usage in specific genes and a conservation at the level of gene architecture rather than primary sequence. CLE-mRNAs display spatio-temporal expression patterns across development where they are associated with ribosomes. Choosing a CLE-mRNA typically abundant in ALS models (ephA4b-CLE) and perceived as purely pathogenic, we unveil its tissue-specific dynamic expression, its translation, and essential role in retinal ganglion cell axon growth and connectivity. Together, these findings redefine cryptic last exons as regulated splice elements, essential for cellular processes, instead of splicing errors limited to disease settings.