PTEN contains a C-terminal motif that binds to various PDZ domain-containing proteins including PSD-95. The PTEN C-terminus is known to mediate synaptic translocation of PTEN during long-term depression (LTD) and amyloid-b-induced synaptic depression. However, it remains unknown whether it regulates other synaptic functions. We compared the transcriptomic profiles of WT and PTEN C-terminus mutant brains (male) at P21. Here, we report genes that are differentially regulated in the mutant mice. This RNA-Seq analysis revealed a total of nine major differentially expressed genes (DEGs) –three upregulated and six downregulated (P < 0.05). Further gene set enrichment analysis (GSEA) of PTEN C-terminus mutant and WT transcriptomes using 5917 gene sets in the C5 (gene ontology) category revealed two strongly enriched gene ontology functions: ribosome biogenesis (positive) and transmembrane transport (negative). Our results provide a comprehensive transcriptome characterization of PTEN C-terminus mutant mice, which would provide a framework of understanding the role PTEN c-terminus in mediating various synaptic –and in larger sense, cellular –functions, and also allow thorough comparative analysis with the results of other PTEN mutant mouse lines. Overall design: Whole brain transcriptome of P21 wild-type and PTEN C-terminus mutant mice.