Wasl, also known as the gene encoding Neural Wiskott-Aldrich syndrome protein (N-WASP), is an actin nucleation promoting factor. It is involved in regulating actin polymerization via the Arp2/3 complex [5]. This function is crucial as it impacts various cellular processes such as cell motility, phagocytosis, and pseudopodia formation, which are important for normal development and immune responses [2,4].

In pancreatic ductal adenocarcinoma (PDAC), pancreas-specific Wasl deletion in two oncogenic Kras-based PDAC mouse models led to increased survival. Loss of Wasl caused cell-autonomous senescence through displacement of N-WASP binding partners, vesicular accumulation of components of the destruction complex, and upregulation of Cdkn1a(p21) [1].

In cervical cancer, lower WASL expression was associated with lower pathological stage, and patients in the high-expression group had worse overall and recurrence-free survival. Knockdown of WASL was correlated with biological processes like glycolysis and TNF-α signaling [3].

In glioblastoma, lower expression of wasla in microglia led to impaired microglial morphology and functions, and restoring wasla expression increased phagocytosis of pre-neoplastic cells and slowed tumor progression [2].

In conclusion, Wasl plays a significant role in multiple disease conditions, especially in cancer. Gene-knockout models have revealed its oncogenic role in PDAC and cervical cancer, and its importance in maintaining microglial functions during glioblastoma initiation. Understanding Wasl's functions through these models provides potential therapeutic targets for these diseases.