Background: The AHNAK2/ERK signaling pathway has been implicated in regulating vascular smooth muscle cell (VSMC) dynamics, which are crucial for vascular repair and the progression of coronary artery disease (CAD). This study aimed to investigate the role of the AHNAK2/ERK pathway in promoting VSMC proliferation and migration and its potential implications for vascular recovery and cardiovascular health, particularly in enhancing physical resilience. Methods: Proliferation and migration of HA-VSMC cell lines were evaluated using CCK-8, MTT, and scratch assays. AHNAK2 expression was manipulated through gene knockdown and overexpression methods. Relative expression levels of AHNAK2 and ERK mRNA were quantified using PCR assays to determine their interaction and signaling effects. Results: Overexpression of AHNAK2 significantly enhanced VSMC proliferation and migration, as evidenced by increased cell viability in MTT and CCK-8 assays and greater wound closure in scratch assays. Conversely, AHNAK2 knockdown reduced these effects, demonstrating its critical role in regulating VSMC activity. Mechanistically, AHNAK2 influenced the activation of the ERK1/2 pathway, with ERK1/2 levels significantly upregulated in AHNAK2-overexpressing cells. This suggests that AHNAK2 facilitates VSMC dynamics through ERK signaling, promoting vascular repair processes. Conclusion: This study reveals that AHNAK2 effectively promotes VSMC proliferation and migration via the ERK1/2 signaling pathway, underscoring its potential role in vascular recovery and the treatment of endothelial injury and CAD. These findings have important implications for cardiovascular rehabilitation, as enhancing vascular resilience may improve physical performance and recovery in individuals with CAD or related conditions. Future research should focus on in vivo models to further elucidate the downstream molecular mechanisms of the AHNAK2/ERK pathway and its broader applications in sports and rehabilitation medicine.