Ceruloplasmin deficiency drives a fusiform-centric lipid-myelin pathology underlying a visual subtype in autism.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by differences in social communication, language impairments, restricted interests, and repetitive stereotyped behaviors []. Its rising prevalence has created substantial social, economic, and healthcare burdens worldwide []. Sensory abnormalities are common in ASD [], yet often underrecognized. Among these, visual processing anomalies are particularly relevant to core social deficits in ASD []. Individuals with ASD often display atypical visual behaviors, including light hypersensitivity, local processing bias, and avoidance of eye contact []. These impairments reduce global information integration and hinder social functioning by disrupting facial expression decoding and social intention understanding []. Despite its early onset and clinical significance, investigations on atypical visual processing have focused mainly on ocular anatomy, localized functional MRI (fMRI), and structural MRI (sMRI) [–]. The absence of systematic whole-brain multi-scale and multi-parametric analyses has limited deeper pathophysiological understanding of visual processing anomalies in ASD. Lipids, composing about 50% of the human brain’s dry weight, are essential structural components of neuronal membranes. Disrupted lipid homeostasis is implicated in various neurological disorders [] and may provide both mechanistic insights and diagnostic biomarkers for ASD [, ]. The myelin sheath, with the highest lipid content in the central nervous system (70%–80% dry weight) [], is frequently altered in ASD, and dysmyelination is linked to its pathophysiology [–]. Lipid imbalances influence myelination bidirectionally: deficiency impedes myelin formation, while excess promotes oxidative stress and myelin damage []. Elevated cerebral oxidative stress is a potential trigger for ASD []. Mapping interactions between lipid metabolism, myelination, and oxidative stress in specific brain regions could therefore yield novel insights into ASD pathogenesis and early diagnosis.