Abstract: Regulation of neurosteroid biosynthesis is primarily mediated by the steroidogenic acute regulatory (StAR, commonly known as STARD1) protein. The StAR protein, by mobilizing the transport of intramitochondrial cholesterol, mediates the ratelimiting step in neurosteroid biosynthesis. The first steroid produced by the action of cytochrome P450 cholesterol side-chain cleavage enzyme (CYP11A1), at the mitochondrial inner membrane, is pregnenolone (the precursor of all neurosteroids), which is then converted to various steroids by tissue-specific enzymes. The mechanism accounting for the biosynthesis of neuro/steroids involves transcription, translation, or activation of StAR, and these processes are primarily influenced by the cyclic adenosine monophosphate (cAMP)/protein kinase A pathway, in which a plethora of signaling processes play permissible roles. An overwhelming amount of evidence indicates that gain-of-function of StAR enhances the activity of this cholesterol transporter for optimal steroid biosynthesis, and its loss-of-function strikingly decreases steroid hormones (Manna et al., 2024; Manna, 2025). The compelling evidence in the role of StAR in the regulation of steroid biosynthesis has been exemplified by numerous basic and clinical findings. Even so, dysregulation of the steroidogenic machinery, involving the hypothalamic-pituitary-thyroidal-adrenalgonadal system, is common as life progresses from adulthood to senescence, resulting in hormonal and/or neurosteroid deficiencies. Unambiguously, neurosteroidogenesis progressively decreases during the process of aging, leading to a host of pathologies, including Alzheimer’s disease (AD), which is the most prevalent neurodegenerative disorder of geriatric populations (Manna et al., 2023a; Manna, 2025).