The numbers 4, 9, 25, 49, and 121 are squares of consecutive primes: 2^2, 3^2, 5^2, 7^2, and 11^2. The next term should be 13^2 = 169, so 144 is the misfit.
The sequence consists of squares of consecutive prime numbers: 2 squared is 4, 3 squared is 9, 5 squared is 25, and 7 squared is 49. Since 144 is the square of 12, which is not a prime number, it is the misfit in the sequence.