## 12 Current Research Gaps, Future Directions, and Perspectives  
Although enzymes have been used in skincare formulations for several years, significant gaps and limitations still remain. Most studies and clinical trials focus on short-term exfoliation effects, but the long-term skin health impact remains largely unexplored [6]. Key challenges include stability [114], the risk of over-exfoliation and skin irritation [1; 5; 15],variability in enzyme activity due to different extraction and purification methods, and non-standardized pH, temperature, and concentration conditions across plant sources [163]. Additionally, cost and accessibility [44; 45], regulatory hurdles, consumer acceptance [6], and environmental and sustainability concerns [68; 201] must be addressed in order to create efficacious, enzyme-based cosmetic products. In this context, the following section explores future perspectives and potential solutions. The use of proteolytic enzymes in cosmetics is evolving rapidly, driven by advances in science, sustainability, and a deeper understanding of skin biology. The cosmetic industry is continuously growing, and although proteolytic enzymes are already used in various cosmetic products, the field is still expanding with new applications, improved formulations, and cutting-edge technologies. With the rise in biotechnology, bioengineering, and artificial intelligence (AI), proteolytic enzymes in cosmetic products will become \"smarter\", more sustainable, and highly customized. Bromelain's strong exfoliation and calming properties, fiction's gentle exfoliation profile, and papain's deep cleansing and acne treatment characteristics serve as promising cosmetic agents [18; 22; 44; 158]  
One of the most significant trends is the move towards personalized skincare solutions. Advances in biotechnology and genomics enable the creation of skincare products tailored to individual skin types and conditions. Proteolytic enzymes can be customized to provide bespoke exfoliation and treatment options based on a person's unique genetic predispositions to certain skin conditions, such as acne, hyperpigmentation, and issues like sensitivity [163; 207]. Smart enzyme-based cosmetics, enzyme diagnostic tools (i.e., biosensors) [208], and Al-powered skin analysis [209], can adapt to environmental changes like temperature or pollution level to optimize skin renewal. Companies are currently shifting their focus towards DNA-based skincare recommendations, where specific enzymes facilitate unique skin needs [163; 207]. Recombinant DNA technology, where genetically engineered microorganisms generate bromelain, fiction, and papain enzymes under controlled, low-impact conditions, has offered high proteolytic enzyme thermal stability, high enzyme yield, and significant proteolytic activity [3; 17]. Enzyme immobilization is also promising in extending usability and reducing waste in cosmetic products [93; 115; 116]. Sustainability and ethical sourcing are also becoming increasingly important in the cosmetic industry. Biotechnology offers innovative methods for genetically producing enzymes via microbial fermentation (i.e., engineered bacteria and fungi), reducing environmental impact compared to traditional extraction methods [210]. Additionally, the shift towards cruelty-free and vegan products is fueling the use of plant-based proteolytic enzymes like bromelain, fiction, and papain, which aligns with such ethical considerations [121]. Their production parameters can be optimized to minimize waste; for instance, by using agricultural by-products (like pineapple stems for bromelain, or papaya or fig peels for papain and fiction) as raw materials, the industry can reduce waste and utilize materials that would otherwise be discarded, enhancing the concept of the circular economy [91; 101; 190]. Many companies in the cosmetic industry currently integrate circular economy principles, including this, by using by-products [158].