HCLS1, also known as hematopoietic cell-specific protein-1 or HS1, is a versatile actin-binding protein in leukocytes. It is homologous to the ubiquitous ABP cortactin in hematopoietic cells. HS1 is crucial for processes like actin remodeling in leukocytes, enabling functions such as adhesion, migration, phagocytosis, and granule release. It is also involved in activating GTPases and integrins, and mediates signaling downstream of receptors like BCR, TCR, and CXCR4 [1].

HCLS1-deficient mice are neutropenic, demonstrating the importance of HCLS1 in myelopoiesis in vivo. In patients with severe congenital neutropenia, mutations in HAX1 (HCLS1-associated protein X-1) lead to defects in G-CSF-triggered phosphorylation of HCLS1, reducing the autoregulation and expression of LEF-1, which is involved in G-CSF-triggered granulopoiesis [2].

In conclusion, HCLS1 is essential for leukocyte-related functions and myelopoiesis. Studies using HCLS1-deficient mice have provided valuable insights into its role in severe congenital neutropenia, highlighting its significance in understanding the pathophysiology of this disease.