ALDH1

Aldehyde dehydrogenase 1 (ALDH1) comprises several isoforms, including ALDH1A1, ALDH1A2, and ALDH1A3, and functions as an NAD(P)+-dependent enzyme family that oxidizes aldehydes and contributes to cellular detoxification, stem cell maintenance, and differentiation programs[1]. Mechanistically, ALDH1 isoforms participate in the synthesis of all-trans retinoic acid (RA) from retinaldehyde, linking ALDH1 activity to retinoid signaling pathways that regulate self-renewal, differentiation, and cellular homeostasis[1][2]. In disease settings, elevated ALDH1 activity is widely associated with cancer stem cells (CSCs) and correlates with tumor initiation, therapeutic resistance, stemness maintenance, and disease progression across multiple solid tumors[1][2]. ALDH1A1 in particular contributes to resistance against oxidative and aldehyde-induced stress and is frequently enriched in drug-resistant cancer cell populations, making it a valuable experimental marker for CSC identification and functional studies[2][3][4]. Compared with related isoforms, ALDH1A1 and ALDH1A3 both regulate aldehyde detoxification and retinoic acid biosynthesis, yet ALDH1A1 is less efficient at generating all-trans retinoic acid than ALDH1A3 and exhibits distinct regulatory interactions with oncogenic pathways[2][5]. For experimental applications, genetic silencing, pharmacological inhibition, and ALDH-targeting strategies are widely used to investigate CSC biology, overcome chemoresistance, and evaluate isoform-specific therapeutic vulnerabilities in cancer models[3][6][7].