Alas1, also known as 5'-aminolevulinate synthase 1, is the rate-limiting enzyme in heme synthesis, a crucial process for maintaining intracellular heme levels [1,2,3,4,5]. Heme is involved in numerous biological processes, such as oxygen transport, electron transfer, and enzyme catalysis. Thus, Alas1 is of great biological importance in various tissues and organisms. Genetic models, like gene knockout mouse models, can be valuable tools to study its function.

In zebrafish, Alas1 -deficient models showed proper neutrophil initiation, but maturation was blocked due to heme deficiency, leading to lipid storage and granule formation deficiencies, as well as loss of heme-dependent granule protein activities, impairing bactericidal ability and augmenting inflammatory responses [3]. In mice, heterozygous disruption of Alas1 caused an accelerated age-dependent reduction in free heme, but not total heme, in skeletal muscle and liver, which could be related to a prediabetic phenotype and mitochondrial abnormality [5]. In cultured cardiomyocytes, doxorubicin decreased Alas1 abundance, disrupting heme synthesis, causing iron overload and ferroptosis, while Alas1 overexpression prevented this outcome [1]. In colorectal cancer cell lines, suppressing Alas1 inhibited cell proliferation and metastasis [4].

In conclusion, Alas1 is essential for heme synthesis, which in turn impacts various biological functions. Studies using gene knockout or knockdown models in zebrafish and mice have revealed its role in neutrophil maturation, age-related heme changes, and disease-related processes like ferroptosis in cardiomyocytes and proliferation/metastasis in colorectal cancer. These findings provide insights into the mechanisms of related diseases and potential therapeutic targets.