The article provides a comprehensive overview of the polyglutamine protein ATXN2, its molecular functions, and its involvement in various diseases. ATXN2, encoded by the *ATXN2* gene, contains a CAG repeat sequence that can expand abnormally, leading to an extended polyQ tract. This expansion alters the protein's conformational dynamics, resulting in toxic gain or partial loss of function. While the primary focus is on spinocerebellar ataxia type 2 (SCA2), intermediate expansions are also linked to amyotrophic lateral sclerosis (ALS) and parkinsonism. ATXN2 plays crucial roles in RNA metabolism, stress granules dynamics, endocytosis, calcium signaling, and circadian rhythm regulation. The expanded ATXN2 is associated with pathological features such as autophagy impairment, RNA-mediated toxicity, increased oxidative stress, and disrupted calcium homeostasis. Despite significant progress, the exact mechanisms remain largely elucidated. The review highlights the complex interplay between ATXN2 and various cellular processes, including its interactions with other proteins and its involvement in disease progression. It also discusses the current therapeutic approaches, which are limited to symptomatic and supportive treatments, and explores potential innovative strategies for addressing the root causes of SCA2.The article provides a comprehensive overview of the polyglutamine protein ATXN2, its molecular functions, and its involvement in various diseases. ATXN2, encoded by the *ATXN2* gene, contains a CAG repeat sequence that can expand abnormally, leading to an extended polyQ tract. This expansion alters the protein's conformational dynamics, resulting in toxic gain or partial loss of function. While the primary focus is on spinocerebellar ataxia type 2 (SCA2), intermediate expansions are also linked to amyotrophic lateral sclerosis (ALS) and parkinsonism. ATXN2 plays crucial roles in RNA metabolism, stress granules dynamics, endocytosis, calcium signaling, and circadian rhythm regulation. The expanded ATXN2 is associated with pathological features such as autophagy impairment, RNA-mediated toxicity, increased oxidative stress, and disrupted calcium homeostasis. Despite significant progress, the exact mechanisms remain largely elucidated. The review highlights the complex interplay between ATXN2 and various cellular processes, including its interactions with other proteins and its involvement in disease progression. It also discusses the current therapeutic approaches, which are limited to symptomatic and supportive treatments, and explores potential innovative strategies for addressing the root causes of SCA2.