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Abstract MicroRNAs are regulators of gene expression and their dysregulation can lead to various diseases. MicroRNA-135 (MiR-135) exhibits brain-specific expression, and performs various functions such as neuronal morphology, neural induction, and synaptic function in the human brain. Dysfunction of miR-135 has been reported in brain tumors, and neurodegenerative and neurodevelopmental disorders. Several reports show downregulation of miR-135 in glioblastoma, indicating its tumor suppressor role in the pathogenesis of brain tumors. In this review, by performing in silico analysis of molecular targets of miR-135, we reveal the significant pathways and processes modulated by miR-135. We summarize the biological significance, roles, and signaling pathways of miRNAs in general, with a focus on miR-135 in different neurological diseases including brain tumors, and neurodegenerative and neurodevelopmental disorders. We also discuss methods, limitations, and potential of glioblastoma organoids in recapitulating disease initiation and progression. We highlight the promising therapeutic potential of miRNAs as antitumor agents for aggressive human brain tumors including glioblastoma.