Despite these housekeeping functions and its ubiquitous expression, we demonstrate that the loss of YME1L in the nervous system of the mouse causes striking cell‐type‐specific deficiencies: Young mice show microphthalmia, cataracts, and retinal inflammation followed by the development of progressive axonal degeneration specifically in the dorso‐lateral column of the spinal cord. Here, YME1L1 is linked to microphthalmia.