The dual role of mTOR signaling in lung development and adult lung diseases.

The architecture of the mammalian lung is both intricate and distinct. The respiratory system consists of a complex network of semirigid airway tubes, stretching from the trachea to the alveoli, highly vascularized sacs responsible for gas exchange. This system demands precise regulation. The mammalian target of rapamycin (mTOR) functions as a receptor and regulatory hub for various cellular processes, including metabolism, proliferation, and autophagy, and plays a pivotal role in lung development and regeneration, continuing to influence cellular processes into early childhood. Over the past decade, studies have identified abnormally elevated mTOR activity in adult lung diseases such as acute lung injury and idiopathic pulmonary fibrosis, leading to the approval of mTOR inhibitors for clinical use. However, during fetal lung development and the postnatal period, mTOR often exhibits a dual role. Its dynamic expression requires careful adaptation to temporal and spatial variations. The safety and efficacy of mTOR inhibitors during these developmental windows remain uncertain, as the role of mTOR becomes increasingly complex in response to the dramatic changes in lung tissue. This review aims to analyze the regulatory mechanisms and functional roles of the mTOR pathway throughout various stages of lung development and adult pulmonary diseases, highlighting the need for caution in using mTOR inhibitors during critical developmental phases. Careful evaluation is essential when considering pharmaceutical interventions for abnormal lung development and pediatric pulmonary disorders.