2017; Xu et al. 2022). Moreover, the role of Ptpro in BDNF signaling and neuroinflammation connects it to established pathways of SUD-related plasticity (Gatto et al. 2013; Zhang et al. 2024). The second candidate, teneurin transmembrane protein 2 (TENM2), has a strong genetic association with nicotine dependence in human GWAS (Quach et al. 2020) and is functionally implicated in substance use, as its suppression in Drosophila has been shown to reduce ethanol consumption (O’Farrell et al. 2023). This evidence concerns the gene PTPRO and nicotine dependence.