Ether phospholipid synthesis has been genetically and physiologically linked to neurodevelopmental diseases like ADHD and autism. However, so far it is unclear whether plasmalogen or non-plasmalogen ether lipid species mediate this association. To address this, we compared two distinct mouse models, namely Gnpat KO and Peds1 KO, and wild-type controls. Glyceronephosphate O-acyltransferase (GNPAT) initiates the formation of the defining ether bond inside peroxisomes; lack of this enzyme abolishes the biosynthesis of all ether lipids. Plasmanylethanolamine desaturase (PEDS1, TMEM189) completes plasmalogen synthesis at the ER by introducing the specific vinyl-ether bond; thus, inactivation of Peds1 leads to the selective loss of plasmalogens. Both mouse models are hyperactive and demonstrate stereotypic behavior. Remarkably, only Gnpat KO but not Peds1-deficient mice showed an impaired marble burying phenotype. On the biochemical level, the amounts of various neurotransmitters were reduced in Gnpat KO brain but indistinguishable from control in Peds1 deficiency. Similarly, when inducing norepinephrine release from hippocampal slices, we observed reduced release in Gnpat KO and normal release in Peds1-deficient slices. Immunohistochemical investigations demonstrated demyelination accompanied by activated microglia and astrocytes only in Gnpat KO mice but not in 16-month-old Peds1 KO mice. Thus, although the loss of vinyl-ether-bonded plasmalogens can apparently be compensated to maintain neurotransmitter and myelin homeostasis, which is impaired in full ether lipid deficiency, plasmalogens are crucial for normal behavior with their absence inducing hyperactivity and stereotypy. Our experiments demonstrate a subclass-specific influence of ether lipid deficiency on behavioral manifestations mimicking neurodevelopmental disorders and on the potential molecular underpinnings.