The human genome exhibits substantial transcriptomic complexity, with prominent alternative promoter usage, splicing, and polyadenylation generating extensive transcript-isoform diversity. Isoform dysregulation has been increasingly implicated in neurodevelopmental and psychiatric disorders (NPDs), yet the landscape, function, and genetic regulation of brain isoforms remain poorly understood, largely due to short-read sequencing limitations. Recent advances in long-read sequencing (LR-seq) now enable scalable full-length transcriptome profiling with developmental and single-cell resolution. Here, I highlight recent progress in isoform discovery, quantification, functional annotation, and genetic regulation, with emphasis on emerging links to human neurodevelopment and disease. Our recent work has leveraged bulk and single-cell LR-seq to profile the developing human brain during peak neurogenesis and uncovered tens of thousands of previously unannotated brain isoforms, with neuronal maturation marked by increased exon inclusion and progressive 3′UTR lengthening. In parallel, we have recently developed isoTWAS, a method for isoform-centric complex trait mapping of genome-wide association (GWAS) results, substantially increasing power for gene discovery and mechanistic interpretation compared with traditional gene-level analyses. Together, these advances establish isoform diversity as a fundamental yet underappreciated axis of brain gene regulation and a key entry point for dissecting neuropsychiatric disease biology.