Lcp2-flox Mouse

Lcp2, also known as lymphocyte cytosolic protein 2 or SLP-76, is a crucial adapter in the SLP-76 family. It is essential for immunoreceptor signaling, such as T-cell receptor signaling, and also required for integrin signaling in neutrophils and platelets. Lcp2 is involved in multiple immune-related pathways and is of great biological importance in T-cell development and activation [2,3].

In a patient with biallelic Lcp2 variants, there was combined immunodeficiency and impaired PI3K signaling. Biallelic variants in Lcp2 impaired neutrophil function and T-cell and B-cell antigen-receptor signaling, causing combined immunodeficiency with early-onset immune dysregulation [4]. In primary human T cells, base-editing mutagenesis identified alleles in Lcp2, including gain-of-function and loss-of-function mutations, which could tune T-cell activation and cytokine production [1]. Also, in metastatic skin cutaneous melanoma, Lcp2 was upregulated and associated with good overall survival, and high Lcp2 expression was positively correlated with more tumor-infiltrating CD8+ T cells [2].

In conclusion, Lcp2 is essential for immune-related signaling pathways, especially in T-cell function. Studies with patients having Lcp2 variants and base-editing mutagenesis in T cells have revealed its role in immunodeficiency and T-cell function modulation. In melanoma, its upregulation and association with tumor-infiltrating CD8+ T cells suggest its importance in anti-tumor immunity.