Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 24 2 2025 03 10 119 131 EN Somayeh Shamlou Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Jafar Kiani Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Zahra Hasanpoor Department of Immunology, School of Medical Science, Tarbiat Modares University, Tehran, Iran Mohammad Tollabi Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran AND Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran Fatemeh Norooznezhad Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Saeedeh Torabi Goudarzi Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Javad Verdi Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran Nasim Vousooghi Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran 2024 05 21 2024 09 10 Natural killer (NK) cells are crucial components of the innate immune system and have emerged as significant players in the pathogenesis of heart diseases. This review discusses recent findings regarding the multifaceted roles of NK cells in various cardiac conditions, including coronary artery disease, myocardial infarction, heart failure, myocarditis, and heart transplantation. It outlines the NK cell subsets, particularly CD56-bright and CD56-dim variations, their functional characteristics, cytokine profiles, and the inflammatory pathways they are involved. The review discusses both the beneficial and detrimental effects of NK cell activity on cardiac pathology by underlining their participation in immune regulation, tissue repair, and graft rejection dynamics. Additionally, we have addressed the impact of NK-cell–oriented environmental signals and discussed potential therapeutic approaches, such as immunomodulatory and anti-inflammatory strategies targeting NK cells. This review was therefore geared towards integrating available studies in understanding NK cell dynamics in heart disease and offering insights for future clinical interventions. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4109 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4109/2154